Potassium Hydroxide → HCID 71073319, compound

HRID 245722Notes

Reaction equation

HRID 245722 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:11][C:12]1[C:13]2[N:14]([C:18]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[N:19][CH:20]=2)[CH:15]=[CH:16][N:17]=1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+].[OH-].[K+]>ClCCl.C(O)(=O)C.CO.O>[CH3:11][C:12]1[C:13]2[N:14]([C:18]([CH:21]3[CH2:26][CH2:25][N:24]([CH:7]4[CH2:8][CH2:9][N:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]4)[CH2:23][CH2:22]3)=[N:19][CH:20]=2)[CH:15]=[CH:16][N:17]=1

Participants

10

Reactant 5

HCID 14797Potassium HydroxideHCID 122563N-Acetyl-4-piperidone2×HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 67364214HCID 67364214, compound

Product 1

HCID 71073319HCID 71073319, compoundYield 63.9%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To 1-acetyl-4-piperidone (0.877 mmol, 0.109 ml) in dichloromethane (3 ml) and acetic acid (0.143 ml) under nitrogen atmosphere was added 8-methyl-3-(piperidin-4-yl)imidazo[1,5-a]pyrazine (0.797 mmol, 172 mg) in dichloromethane (4 ml) and methanol (1 ml). After 20 minutes, sodium cyanoborohydride (0.877 mmol, 55.1 mg) was added. After stirring at room temperature for one hour 1-acetyl-4-piperidone (0.877 mmol, 0.109 ml) and acetic acid (0.05 ml) were added. After 1.5 hours water was added to the reaction mixture and saturated aqueous sodium hydrogencarbonate solution were added to the water layer and made basic (pH 10) with potassium hydroxide. This aqueous basic mixture was extracted with dichloromethane/methanol (9/1) and the organic extracts concentrated in vacuo. The residue was purified by column chromatography (silica gel; dichloromethane containing 1% triethylamine with gradient 0 to 10% of methanol) to give 1-(4-(8-methylimidazo[1,5-a]pyrazin-3-yl)-1,4′-bipiperidin-1′-yl)ethanone (174 mg).

Workup

  1. additionwere added
  2. extractionThis aqueous basic mixture was extracted with dichloromethane/methanol (9/1)
  3. concentrationthe organic extracts concentrated in vacuo
  4. customThe residue was purified by column chromatography (silica gel; dichloromethane containing 1% triethylamine with gradient 0 to 10% of methanol)

Sources & evidence

ORD record
ord-d62e34c990c34306b7fc141c412a55ce
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

Loading…